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Inhibitory effects of endogenous and exogenous interferon‐γ on bronchial hyperresponsiveness, allergic inflammation and T‐helper 2 cytokines in Brown–Norway rats
Author(s) -
Huang Tj,
MacAry Pa,
T Wilke,
Kemeny Dm,
Kian Fan Chung
Publication year - 1999
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1999.00870.x
Subject(s) - immunology , eosinophil , ovalbumin , cytokine , bronchial hyperresponsiveness , interferon gamma , bronchoalveolar lavage , interleukin 5 , eosinophilia , medicine , interleukin 4 , cd8 , interleukin , immune system , asthma , respiratory disease , lung
Interferon‐γ (IFN‐γ) is an important cytokine involved in the regulation of allergen‐induced immune responses. We examined the role of IFN‐γ in a Brown–Norway rat model of bronchial hyperresponsiveness (BHR) and airway eosinophilia, and its effects on the mRNA expression of T helper type 1 (Th1)/Th2 cytokine. Ovalbumin (OA)‐sensitized animals were given either exogenous IFN‐γ (10 5 U/rat over 3 days, intraperitoneally) or anti‐IFN‐γ blocking antibody (DB‐1 0·3 mg/rat, intravenously) prior to exposure to OA aerosol and were studied 18–24 hr later. In sensitized animals, OA induced significant BHR, accumulation of eosinophils, T lymphocytes and neutrophils in bronchoalveolar lavage (BAL) fluid, and also increased eosinophils and CD8 + T cells in the airways. Exogenous IFN‐γ attenuated allergen‐induced BHR ( P <0·02, compared with sham‐treated animals) together with a significant reduction in eosinophil and neutrophil numbers in BAL fluid ( P <0·005), and eosinophils and CD8 + T cells in airways ( P <0·05). By contrast, anti‐IFN‐γ antibody increased airway CD4 + T cells and BHR. Using reverse transcriptase–polymerase chain reaction, significant increases in Th2 [interleukin‐4 (IL‐4), IL‐5 and IL‐10], and IFN‐γ cytokine mRNA were found in the lungs of sensitized and OA‐exposed animals, while exogenous IFN‐γ significantly suppressed IL‐4, IL‐5 and IL‐10 mRNA expression, and anti‐IFN‐γ antibody increased IL‐4 and IL‐5 mRNA expression. These results indicate that Th1 effects, such as those mediated by IFN‐γ, play a down‐regulatory role to suppress the Th2 responses associated with allergen‐induced BHR and eosinophilic inflammation.